This invention relates to the treatment of ruminal lactic acidosis in ruminant animals. Specifically, this invention relates to the use of alpha-2 adrenoceptor antagonists in the treatment of ruminant animals suffering from ruminal lactic acidosis.
One embodiment of this invention is directed towards the restoration by alpha-2 adrenoceptor antagonists of forestomach contractions in ruminants with ruminal stasis (forestomach atony) or forestomach hypomotility caused by ruminal lactic acidosis. Another embodiment of this invention is directed towards the overall use of alpha-2 adrenoceptor antagonists in the treatment of ruminant animals suffering from ruminal lactic acidosis.
Ruminal lactic acidosis (also referred to as grain overload, rumen overload, carbohydrate engorgement, feedlot founder or D-lactic acidosis) develops in ruminant animals following the ingestion of large amounts of unaccustomed feeds that are rich in readily fermentable carbohydrates. This disease occurs most commonly in ruminant livestock, for example, sheep, feedlot cattle and dairy cows, that are maintained on high energy rations. Characteristic symptoms of this disease include systemic acidosis, (decreased blood pH), ruminal acidosis, (decreased pH of rumen contents), ruminal stasis or forestomach hypomotility, inappetence, depression, and hemoconcentration. These symptoms, reportedly, result from the accumulation of toxic levels of non-metabolized D-lactic acid that are produced by abnormal fermentation in the forestomach. At present, the recommended treatments for this disease involve ruminal lavage and/or rumenotomy and intravenous infusions of bicarbonate to correct the systemic acidosis.
Many members of the family of compounds known as alpha-2 adrenoceptor antagonists have been reported in the prior art to function as antidepressants and antihypertensives (see U.S. Pat. Nos.: 4,710,504; 4,686,226; 4,616,017; 4,652,642; 4,640,924; 4,717,731); and have been proposed in the treatment of asthma, diabetes and migraine (see Patents: EP-247764A, J62289566-A); as well as in the treatment of diarrhoea (see Canadian Patent 1,156,147 dated Nov. 1, 1983). However, none of these compounds have, previously, been reported to restore contractions of the forestomach of ruminant animals that are experiencing ruminal stasis or forestomach hypomotility caused by ruminal lactic acidosis, nor have these compounds been proposed for the treatment of ruminants suffering from ruminal lactic acidosis.
Another approach to this problem has been disclosed in U.S. Pat. Nos. 4,112,069 and 4,172,127. In the method of these prior arts, the microorganism Peptococcus asaccharolyticus was introduced into the rumen of a ruminant animal Such an animal will be substantially immediately adapted to the high energy ration or diet employed for fattening, with substantial reduction or elimination of ruminal lactic acidosis which usually occurs when a ruminant animal is abruptly supplied with and maintained on a high-energy ration or feed.
It has now been discovered that a family of compounds (alpha-2 adrenoceptor antagonists) has the ability to re-establish forestomach motility that has been lost or severely diminished in ruminants suffering from ruminal lactic acidosis These compounds have also been found to be effective in the treatment of ruminants experiencing ruminal lactic acidosis.